Nitin Phadnis
Nitin Phadnis
Nitin was born in Mumbai, India and grew up in the nearby city of Pune. As an undergraduate student in Microbiology, he studied novel culturing methods for bacteria and spent his summers playing cricket and hiking the Himalayas studying rotifer biodiversity. After three years of undergraduate studies, he joined the Indian Institute of Science, Bangalore as an Integrated PhD student in Biology. He then joined University of Rochester, NY to pursue his PhD in the laboratory of Allen Orr and was co-advised by Jim Fry. His thesis focused on the genetics of speciation and the molecular basis of dominance. Nitin joined Harmit Malik's laboratory as a post-doctoral fellow in October 2008 where he is now a Howard Hughes Medical Institute fellow of the Life Sciences Research Foundation. He has many broad interests in evolutionary biology and enjoys taking approaches that combine genetics with cell and molecular biology. In his free time, Nitin loves to go camping and hiking with his wife Naina and his daughter Sahana.
Research Interests:
Functional consequences of positive selection:
Advances in whole genome sequencing technologies and population genetic methods to detect selection in genome-wide studies have revealed several classes of genes that evolve rapidly under positive selection. While detecting selection at genomic locations has become easier, a detailed understanding of the evolutionary causes and the functional consequences of the rapid divergence of genes is often missing. In the Malik laboratory, Nitin is pursuing molecular studies of a variety of interesting pathways that evolve rapidly under positive selection, including components of the nuclear transport pathway, dosage compensation proteins and the anti-viral RNA interference machinery in Drosophila.
Speciation:
Nitin is interested in the genetics of hybrid sterility, which is one of the earliest reproductive barriers to evolve between isolated populations. While in Allen Orr's laboratory, Nitin studied the genetics of sterility of hybrid males between the USA and Bogota sub-species of Drosophila pseudoobscura. F1 hybrid males between these sub-species are mostly sterile but, when aged, produce a few progeny that are almost all daughters due to sex chromosome segregation distortion. During his graduate work, Nitin showed that a single gene, Overdrive, causes both hybrid sterilty and segregation distortion in these males, providing evidence that genetic conflict involving segregation distorters may play an important role in the evolution of hybrid sterility. In the Malik laboratory, Nitin continues to study speciation through 1) a cell biological approach to understand the molecular basis of hybrid sterility, and 2) through mapping studies to understand the genetic architecture of F1 hybrid male sterility.
Molecular basis of dominance:
Most deleterious mutations are recessive. The founders of the modern synthesis - Fisher, Wright, Haldane and Muller - realised that the recessivity of mutations doesn't necessarily have to be so. The debate about dominance appeared finally settled by Kacser and Burn's paradigmatic theory that used enzyme kinetics to explain the recessivity of mutations as an inherent consequence of long metabolic pathways. A key prediction of Kacser and Burns' metabolic theory is a negative correlation between the homozygous effects and dominance of mutations. In collaboration with Jim Fry, Nitin studied data on gene deletions in Saccharomyces cerevisiae to test this prediction. Consistent with the metabolic theory, a strong negative correlation exists between the homozygous effects and dominance of mutations. Surprisingly, such a correlation exists not just for enzymes but also for mutations in all classes of genes, indicating that the metabolic theory in its present form may not be a complete explanation for dominance. Nitin continues to develop projects that test different explanations for dominance.
Publications:
2011 Phadnis, N., Hsieh, E. and Malik, H.S. Birth, death and replacement of importins in Drosophila. Molecular Biology and Evolution doi:10.1093/molbev/msr306.
2011 Phadnis, N. Genetic architecture of male sterility and segregation distortion in Drosophila pseudoobscura Bogota-USA hybrids. Genetics 189 (3):1001-1009.
2009 Oliver PL, Goodstadt L, Bayes JJ, Birtle Z, Roach KC, Phadnis N, Beatson SA, Lunter G, Malik HS, Ponting CP. Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa. PLoS Genetics, Dec; 5(12):e1000753. Epub 2009 Dec 4.
2009 Phadnis, N. and Orr, H.A.. A single gene causes both male sterility and segregation distortion in Drosophila hybrids. Science, 323: 376-378.
(Featured in "Perspectives" piece by John Willis, pg 350-351; "Research Highlights" in Nature Genetics, 1 Feb 2009 pg 147; "Research Highlight" in Nature Reviews Genetics, Feb 2009 pg 72; Faculty of 1000)
2007 Orr, H.A., Masly, J.P and Phadnis, N. Speciation in Drosophila: from genes to molecules. Journal of Heredity 98(2): 103-110
2005 Phadnis, N. and Fry, J.D. Widespread correlations between dominance and homozygous effects of mutations: Implications for theories of dominance. Genetics 171: 385-392.
2004 Fry, J.D., Bahnck, C.M., Mikucki, M., Phadnis, N., and W.C. Slattery. Dietary ethanol mediates selection on aldehyde dehydrogenese activity in Drosophila melanogaster. Integrative and Comparative Biology 44:275-283.
2000 Watve, M., Shejval, V., Sonawane, C., Rahalkar, M., Matapurkar, A., Shouche, Y., Patole, M., Phadnis, N., and 5 other authors. The ‘K’ selected oligophilic bacteria: a key to uncultured diversity? Current Science 78:1535-1542.
